Levoxyl Information
Levoxyl () Description
–Levoxyl () (levothyroxine sodium tablets, USP) contain synthetic crystalline L-3,3’,5,5’-tetraiodothyronine sodium salt [levothyroxine (T) sodium]. Synthetic T is identical to that produced in the human thyroid gland. Levothyroxine (T) sodium has an empirical formula of CHIN NaO • HO, molecular weight of 798.86 g/mol (anhydrous), and structural formula as shown:
Microcrystalline cellulose, croscarmellose sodium and magnesium stearate. The following are the coloring additives per tablet strength:
Levoxyl () Clinical Pharmacology
Thyroid hormone synthesis and secretion is regulated by the hypothalamic-pituitary-thyroid axis. Thyrotropin-releasing hormone (TRH) released from the hypothalamus stimulates secretion of thyroid-stimulating hormone, TSH, from the anterior pituitary. TSH, in turn, is the physiologic stimulus for the synthesis and secretion of thyroid hormones, L-thyroxine (T) and L-triiodothyronine (T), by the thyroid gland. Circulating serum T and T levels exert a feedback effect on both TRH and TSH secretion. When serum T and T levels increase, TRH and TSH secretion decrease. When thyroid hormone levels decrease, TRH and TSH secretion increase.
The mechanisms by which thyroid hormones exert their physiologic actions are not completely understood, but it is thought that their principal effects are exerted through control of DNA transcription and protein synthesis. T and T diffuse into the cell nucleus and bind to thyroid receptor proteins attached to DNA. This hormone nuclear receptor complex activates gene transcription and synthesis of messenger RNA and cytoplasmic proteins.
Thyroid hormones regulate multiple metabolic processes and play an essential role in normal growth and development, and normal maturation of the central nervous system and bone. The metabolic actions of thyroid hormones include augmentation of cellular respiration and thermogenesis, as well as metabolism of proteins, carbohydrates and lipids. The protein anabolic effects of thyroid hormones are essential to normal growth and development.
The physiologic actions of thyroid hormones are produced predominately by T, the majority of which (approximately 80%) is derived from T by deiodination in peripheral tissues.
Levothyroxine, at doses individualized according to patient response, is effective as replacement or supplemental therapy in hypothyroidism of any etiology, except transient hypothyroidism during the recovery phase of subacute thyroiditis.
Levothyroxine is also effective in the suppression of pituitary TSH secretion in the treatment or prevention of various types of euthyroid goiters, including thyroid nodules, Hashimoto’s thyroiditis, multinodular goiter and, as adjunctive therapy in the management of thyrotropin-dependent well-differentiated thyroid cancer (see ).
Levoxyl () Indications And Usage
Levothyroxine sodium is used for the following indications:
Levoxyl () Contraindications
Levothyroxine is contraindicated in patients with untreated subclinical (suppressed serum TSH level with normal T and T levels) or overt thyrotoxicosis of any etiology and in patients with acute myocardial infarction. Levothyroxine is contraindicated in patients with uncorrected adrenal insufficiency since thyroid hormones may precipitate an acute adrenal crisis by increasing the metabolic clearance of glucocorticoids (see ). Levoxyl () is contraindicated in patients with hypersensitivity to any of the inactive ingredients in Levoxyl () tablets (see , ).
Levoxyl ()
Levoxyl () Precautions
Levothyroxine has a narrow therapeutic index. Regardless of the indication for use, careful dosage titration is necessary to avoid the consequences of over- or under-treatment. These consequences include, among others, effects on growth and development, cardiovascular function, bone metabolism, reproductive function, cognitive function, emotional state, gastrointestinal function, and on glucose and lipid metabolism. Many drugs interact with levothyroxine sodium necessitating adjustments in dosing to maintain therapeutic response (see ).
Effects on bone mineral density
— Exercise caution when administering levothyroxine to patients with nontoxic diffuse goiter or nodular thyroid disease in order to prevent precipitation of thyrotoxicosis (see ). If the serum TSH is already suppressed, levothyroxine sodium should not be administered (see )
Associated endocrine disorders
General
The diagnosis of hypothyroidism is confirmed by measuring TSH levels using a sensitive assay (second generation assay sensitivity ≤0.1 mIU/L or third generation assay sensitivity ≤0.01 mIU/L) and measurement of free-T.
The adequacy of therapy is determined by periodic assessment of appropriate laboratory tests and clinical evaluation. The choice of laboratory tests depends on various factors including the etiology of the underlying thyroid disease, the presence of concomitant medical conditions, including pregnancy, and the use of concomitant medications (see and ). Persistent clinical and laboratory evidence of hypothyroidism despite an apparent adequate replacement dose of Levoxyl () may be evidence of inadequate absorption, poor compliance, drug interactions, or decreased T potency of the drug product.
Adults
In adult patients with primary (thyroidal) hypothyroidism, serum TSH levels (using a sensitive assay) alone may be used to monitor therapy. The frequency of TSH monitoring during levothyroxine dose titration depends on the clinical situation but it is generally recommended at 6—8 week intervals until normalization. For patients who have recently initiated levothyroxine therapy and whose serum TSH has normalized or in patients who have had their dosage or brand of levothyroxine changed, the serum TSH concentration should be measured after 8—12 weeks. When the optimum replacement dose has been attained, clinical (physical examination) and biochemical monitoring may be performed every 6—12 months, depending on the clinical situation, and whenever there is a change in the patient’s status. It is recommended that a physical examination and a serum TSH measurement be performed at least annually in patients receiving Levoxyl () (see , and ).
Pediatrics
In patients with congenital hypothyroidism, the adequacy of replacement therapy should be assessed by measuring both serum TSH (using a sensitive assay) and total- or free- T. During the first three years of life, the serum total- or free- T should be maintained at all times in the upper half of the normal range. While the aim of therapy is to also normalize the serum TSH level, this is not always possible in a small percentage of patients, particularly in the first few months of therapy. TSH may not normalize due to a resetting of the pituitary-thyroid feedback threshold as a result of hypothyroidism. Failure of the serum T to increase into the upper half of the normal range within 2 weeks of initiation of Levoxyl () therapy and/or of the serum TSH to decrease below 20 mU/L within 4 weeks should alert the physician to the possibility that the child is not receiving adequate therapy. Careful inquiry should then be made regarding compliance, dose of medication administered, and method of administration prior to raising the dose of Levoxyl () .
The recommended frequency of monitoring of TSH and total or free T in children is as follows: at 2 and 4 weeks after the initiation of treatment; every 1—2 months during the first year of life; every 2—3 months between 1 and 3 years of age; and every 3 to 12 months thereafter until growth is completed. More frequent intervals of monitoring may be necessary if poor compliance is suspected or abnormal values are obtained. It is recommended that TSH and T levels, and a physical examination, if indicated, be performed 2 weeks after any change in Levoxyl () dosage. Routine clinical examination, including assessment of mental and physical growth and development, and bone maturation, should be performed at regular intervals (see and ).
Secondary (pituitary) and tertiary (hypothalamic) hypothyroidism
Adequacy of therapy should be assessed by measuring serum free-T levels ,which should be maintained in the upper half of the normal range in these patients.
Many drugs affect thyroid hormone pharmacokinetics and metabolism (e.g., absorption, synthesis, secretion, catabolism, protein binding, and target tissue response) and may alter the therapeutic response to Levoxyl () . In addition, thyroid hormones and thyroid status have varied effects on the pharmacokinetics and action of other drugs. A listing of drug-thyroidal axis interactions is contained in Table 2.
The list of drug-thyroidal axis interactions in Table 2 may not be comprehensive due to the introduction of new drugs that interact with the thyroidal axis or the discovery of previously unknown interactions. The prescriber should be aware of this fact and should consult appropriate reference sources. (e.g., package inserts of newly approved drugs, medical literature) for additional information if a drug-drug interaction with levothyroxine is suspected.
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Consumption of certain foods may affect levothyroxine absorption thereby necessitating adjustments in dosing. Soybean flour (infant formula), cotton seed meal, walnuts, and dietary fiber may bind and decrease the absorption of levothyroxine sodium from the GI tract.
Studies in women taking levothyroxine sodium during pregnancy have not shown an increased risk of congenital abnormalities. Therefore, the possibility of fetal harm appears remote. Levoxyl () should not be discontinued during pregnancy and hypothyroidism diagnosed during pregnancy should be promptly treated.
Hypothyroidism during pregnancy is associated with a higher rate of complications, including spontaneous abortion, pre-eclampsia, stillbirth and premature delivery. Maternal hypothyroidism may have an adverse effect on fetal and childhood growth and development. During pregnancy, serum T levels may decrease and serum TSH levels increase to values outside the normal range. Since elevations in serum TSH may occur as early as 4 weeks gestation, pregnant women taking Levoxyl () should have their TSH measured during each trimester. An elevated serum TSH level should be corrected by an increase in the dose of Levoxyl () . Since postpartum TSH levels are similar to preconception values, the Levoxyl () dosage should return to the pre-pregnancy dose immediately after delivery. A serum TSH level should be obtained 6—8 weeks postpartum.
Thyroid hormones do not readily cross the placental barrier; however, some transfer does occur as evidenced by levels in cord blood of athyreotic fetuses being approximately one-third maternal levels. Transfer of thyroid hormone from the mother to the fetus, however, may not be adequate to prevent in utero hypothyroidism.
General
The goal of treatment in pediatric patients with hypothyroidism is to achieve and maintain normal intellectual and physical growth and development.
The initial dose of levothyroxine varies with age and body weight (see ). Dosing adjustments are based on an assessment of the individual patient’s clinical and laboratory parameters (see ).
In children in whom a diagnosis of permanent hypothyroidism has not been established, it is recommended that levothyroxine administration be discontinued for a 30-day trial period, but only after the child is at least 3 years of age. Serum T and TSH levels should then be obtained. If the T is low and the TSH high, the diagnosis of permanent hypothyroidism is established, and levothyroxine therapy should be reinstituted. If the T and TSH levels are normal, euthyroidism may be assumed and, therefore, the hypothyroidism can be considered to have been transient. In this instance, however, the physician should carefully monitor the child and repeat the thyroid function tests if any signs or symptoms of hypothyroidism develop. In this setting, the clinician should have a high index of suspicion of relapse. If the results of the levothyroxine withdrawal test are inconclusive, careful follow-up and subsequent testing will be necessary.
Since some more severely affected children may become clinically hypothyroid when treatment is discontinued for 30 days, an alternate approach is to reduce the replacement dose of levothyroxine by half during the 30-day trial period. If, after 30 days, the serum TSH is elevated above 20 mU/L, the diagnosis of permanent hypothyroidism is confirmed, and full replacement therapy should be resumed. However, if the serum TSH has not risen to greater than 20mU/L, levothyroxine treatment should be discontinued for another 30-day trial period followed by repeat serum T and TSH.
The presence of concomitant medical conditions should be considered in certain clinical circumstances and, if present, appropriately treated (see ).
Congenital Hypothyroidism (see and
Rapid restoration of normal serum T concentrations is essential for preventing the adverse effects of congenital hypothyroidism on intellectual development as well as on overall physical growth and maturation. Therefore, Levoxyl () therapy should be initiated immediately upon diagnosis and is generally continued for life.
During the first 2 weeks of Levoxyl () therapy, infants should be closely monitored for cardiac overload, arrhythmias, and aspiration from avid suckling.
The patient should be monitored closely to avoid undertreatment or overtreatment. Undertreatment may have deleterious effects on intellectual development and linear growth. Overtreatment has been associated with craniosynostosis in infants, and may adversely affect the tempo of brain maturation and accelerate the bone age with resultant premature closure of the epiphyses and compromised adult stature.
Acquired Hypothyroidism in Pediatric Patients
The patient should be monitored closely to avoid undertreatment and overtreatment. Undertreatment may result in poor school performance due to impaired concentration and slowed mentation and in reduced adult height. Overtreatment may accelerate the bone age and result in premature epiphyseal closure and compromised adult stature.
Treated children may manifest a period of catch-up growth, which may be adequate in some cases to normalize adult height. In children with severe or prolonged hypothyroidism, catch-up growth may not be adequate to normalize adult height.
Levoxyl () Adverse Reactions
Adverse reactions associated with levothyroxine therapy are primarily those of hyperthyroidism due to therapeutic overdosage. They include the following:
Pseudotumor cerebri and slipped capital femoral epiphysis have been reported in children receiving levothyroxine therapy. Overtreatment may result in craniosynostosis in infants and premature closure of the epiphyses in children with resultant compromised adult height.
Seizures have been reported rarely with the institution of levothyroxine therapy.
Inadequate levothyroxine dosage will produce or fail to ameliorate the signs and symptoms of hypothyroidism.
Hypersensitivity reactions to inactive ingredients have occurred in patients treated with thyroid hormone products. These include urticaria, pruritus, skin rash, flushing, angioedema, various GI symptoms (abdominal pain, nausea, vomiting and diarrhea), fever, arthralgia, serum sickness and wheezing. Hypersensitivity to levothyroxine itself is not known to occur.
In addition to the above events, the following have been reported, predominately when Levoxyl () tablets were not taken with water: choking, gagging, tablet stuck in throat and dysphagia (see ).
Levoxyl () Overdosage
The signs and symptoms of overdosage are those of hyperthyroidism (see and ). In addition, confusion and disorientation may occur. Cerebral embolism, shock, coma, and death have been reported. Seizures have occurred in a child ingesting approximately 20 mg of levothyroxine. Symptoms may not necessarily be evident or may not appear until several days after ingestion of levothyroxine sodium.
Levoxyl () Dosage And Administration
The goal of replacement therapy is to achieve and maintain a clinical and biochemical euthyroid state. The goal of suppressive therapy is to inhibit growth and/or function of abnormal thyroid tissue. The dose of Levoxyl () that is adequate to achieve these goals depends on a variety of factors including the patient’s age, body weight, cardiovascular status, concomitant medical conditions, including pregnancy, concomitant medications, and the specific nature of the condition being treated (see and ). Hence, the following recommendations serve only as dosing guidelines. Dosing must be individualized and adjustments made based on periodic assessment of the patient’s clinical response and laboratory parameters (see ).
The Levoxyl () should be taken in the morning on an empty stomach, at least one-half hour before any food is eaten. Levoxyl () should be taken at least 4 hours apart from drugs that are known to interfere with its absorption (see ).
Levoxyl () should be taken with water (see and ).
Due to the long half-life of levothyroxine, the peak therapeutic effect at a given dose of levothyroxine sodium may not be attained for 4—6 weeks.
Caution should be exercised when administering Levoxyl () to patients with underlying cardiovascular disease, to the elderly, and to those with concomitant adrenal insufficiency (see ).
For most patients older than 50 years or for patients under 50 years of age with underlying cardiac disease, an initial starting dose of of levothyroxine sodium is recommended, with gradual increments in dose at 6—8 week intervals, as needed. The recommended starting dose of levothyroxine sodium in elderly patients with cardiac disease is , with gradual dose increments at 4—6 week intervals. The levothyroxine sodium dose is generally adjusted in 12.5—25 mcg increments until the patient with primary hypothyroidism is clinically euthyroid and the serum TSH has normalized.
In patients with severe hypothyroidism, the recommended initial levothyroxine sodium dose is with increases of 25 mcg/day every 2—4 weeks, accompanied by clinical and laboratory assessment, until the TSH level is normalized.
In patients with secondary (pituitary) or tertiary (hypothalamic) hypothyroidism, the levothyroxine sodium dose should be titrated until the patient is clinically euthyroid and the serum free-T level is restored to the upper half of the normal range.
Pediatric Dosage — Congenital or Acquired Hypothyroidism (see )
Levoxyl () How Supplied
Levoxyl ()
Levoxyl () Principal Display Panel-mcg
NDC 60793-850-01
(levothyroxine sodium tablets, USP)
100 Tablets
Each tablet contains 25 mcg levothyroxine sodium
King
Levoxyl () Principal Display Panel-mcg
NDC 60793-851-01 (KING)
(levothyroxine sodium tablets, USP)
100 Tablets
Each tablet contains 50 mcg levothyroxine sodium
King
Levoxyl () Principal Display Panel-mcg
NDC 60793-852-01
(levothyroxine sodium tablets, USP)
100 Tablets
Each tablet contains 75 mcg levothyroxine sodium
King
Levoxyl () Principal Display Panel-mcg
NDC 60793-853-01
(levothyroxine sodium tablets, USP)
100 Tablets
Each tablet contains 88 mcg levothyroxine sodium
King
Levoxyl () Principal Display Panel-mcg
NDC 60793-854-01
(levothyroxine sodium tablets, USP)
100 Tablets
Each tablet contains 100 mcg levothyroxine sodium
King
Levoxyl () Principal Display Panel-mcg
NDC 60793-855-01
(levothyroxine sodium tablets, USP)
100 Tablets
Each tablet contains 112 mcg levothyroxine sodium
King
Levoxyl () Principal Display Panel-mcg
NDC 60793-856-01
(levothyroxine sodium tablets, USP)
100 Tablets
Each tablet contains 125 mcg levothyroxine sodium
King
Levoxyl () Principal Display Panel-mcg
NDC 60793-857-01
(levothyroxine sodium tablets, USP)
100 Tablets
Each tablet contains 137 mcg levothyroxine sodium
King
Levoxyl () Principal Display Panel-mcg
NDC 60793-858-01
(levothyroxine sodium tablets, USP)
100 Tablets
Each tablet contains 150 mcg levothyroxine sodium
King
Levoxyl () Principal Display Panel-mcg
NDC 60793-859-01
(levothyroxine sodium tablets, USP)
100 Tablets
Each tablet contains 175 mcg levothyroxine sodium
King
Levoxyl () Principal Display Panel-mcg
NDC 60793-860-01
(levothyroxine sodium tablets, USP)
100 Tablets
Each tablet contains 200 mcg levothyroxine sodium
King
